PK-directed Intravenous Busulfan in Combination with High-Dose Melphalan and Bortezomib as a Conditioning Regimen for Patients with Multiple Myeloma

Publication date: Available online 17 June 2017 Source:Clinical Lymphoma Myeloma and Leukemia Author(s): Stefan K. Barta, Rishi Jain, Amithaba Mazumder, Jason Carter, Lawrence Almanzar, Roy Browne, Samira Shahnaz, Richard Elkind, David Kaminetzky, Ramakrishna Battini, Olga Derman, Noah Kornblum, Amit Verma, Ira Braunschweig High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m2 (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). We conducted a prospective phase 2 study to investigate the safety and efficacy of conditioning with PK directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM x min. Patients received Btz (1 mg/m2 x 4 doses) and Mel (140 mg/m2). A total of 19 subjects were enrolled. Median age was 55 and median follow-up was 23.7 months. The PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 +/- 2500 μM X min. The overall response rate (ORR) at day +100 post-ASCT was 100% in the evaluable patients with 11% of patients achieving a complete response (CR). The 2-year PFS was 57.9% (95% CI, 38-89) and the 2-year OS was 88.5% (95% CI, 76-100). The most common grade 3 and 4 toxicities w...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research